The　quantitative　and　ultrasensitive　detection　of　amyloid-beta　peptides　Aβ40in　blood　is　considered　as　a　powerful　strategy　for　early　screening　of　Alzheimer’s　disease　(AD).　In　this　study,　combining　dual-aptamer　recognition　and　magnetic-induced　enrichment,　a　background-free　surface-enhanced　Raman　scattering　(SERS)　platform　had　been　developed　for　efficient　Aβ40detection.　Au@Ag-4-ethynylaniline@Au　nanoparticles　(Au@Ag-4-EA@Au　NPs)　had　been　designed　and　modified　on　aptamer2　of　Aβ40to　form　Au@Ag@4-EA@Au-Apt2　(SERS　probe).　4-EA　functionalization　enables　the　use　of　the　Raman　silent　region　(1800–2800　cm–1),　thereby　minimizing　biological　interference　and　avoiding　spectral　overlapping.　The　nanogap　within　gold　and　silver　nanoshells　serves　as　a　strong　plasmonic　enhancer,　significantly　amplifying　the　Raman　signal　and　improving　detection　sensitivity.　Aptamer1　of　Aβ40was　modified　on　a　streptavidin-modified　magnetic　bead　(SA-MB)　to　form　SA-MB-Apt1　(capture　probe).　The　presence　of　the　target　results　in　the　formation　of　the　sandwich　structure　of　SA-MB-Apt1/Aβ40/Apt2-Au@Ag-4-EA@Au　NPs.　Two　Aβ40-specific　aptamers　ensured　precise　biomarker　recognition　and　quantification.　Magnetic-induced　assembly　enriches　Aβ40molecules　and　generates　abundant　plasmonic　＇hot　spots＇　through　nanoparticle　aggregation,　resulting　in　signal　amplification.　The　results　demonstrate　a　remarkable　limit　of　detection　of　25　fM　(S/N　=　3),　with　a　linear　range　from　10–1to　104pM.　This　SERS　platform　provides　a　robust　tool　for　early　AD　diagnosis　and　demonstrates　broad　potential　in　clinical　molecular　diagnostics.　©　2025　American　Chemical　Society